Therapeutic Advances in Chronic Disease最新文献

Background: Elevated arterial stiffness in patients with primary aldosteronism (PA) can be reversed after adrenalectomy; however, the effect of medical treatment with mineralocorticoid receptor antagonist (MRAs) is unknown.

Objectives: The aim of this study was to evaluate the effect of MRAs and compare both treatment strategies on arterial stiffness in PA patients.

Design: Prospective cohort study.

Methods: We prospectively enrolled PA patients from 2006 to 2019 who received either adrenalectomy or MRA treatment (spironolactone). We compared their baseline and 1-year post-treatment biochemistry characteristics and arterial pulse wave velocity (PWV) to verify the effects of treatment and related determinant factors.

Results: A total 459 PA patients were enrolled. After 1:1 propensity score matching for age, sex and blood pressure (BP), each group had 176 patients. The major determinant factors of baseline PWV were age and baseline BP. The adrenalectomy group had greater improvements in BP, serum potassium level, plasma aldosterone concentration, and aldosterone-to-renin ratio. The MRA group had a significant improvement in PWV after 1 year of treatment (1706.2 ± 340.05 to 1613.6 ± 349.51 cm/s, p < 0.001). There were no significant differences in post-treatment PWV (p = 0.173) and improvement in PWV (p = 0.579) between the adrenalectomy and MRA groups. The determinant factors for an improvement in PWV after treatment were hypertension duration, baseline PWV, and the decrease in BP.

Conclusion: The PA patients who received medical treatment with MRAs had a significant improvement in arterial stiffness. There was no significant difference in the improvement in arterial stiffness between the two treatment strategies.

Background: Thyroid hormones are known to regulate bone metabolism and may influence bone mineral density (BMD), as well as the risk of osteoporosis (OP) and fractures in patients with type 2 diabetes mellitus (T2DM). Recently, sensitivity to thyroid hormone indices has been linked with T2DM and OP independently. However, the relationship between thyroid hormone sensitivity and OP in euthyroid T2DM patients has yet to be investigated.

Objectives: The aim of this study was to determine the association between sensitivity to thyroid hormone indices and the risk of OP in euthyroid patients with T2DM.

Design: This study employed a retrospective, cross-sectional design and utilized data acquired from the Cangzhou Central Hospital in China between 2019 and 2020.

Methods: We retrospectively analyzed the data of 433 patients with T2DM for anthropometric measurements, clinical laboratory test results, and BMD. The thyroid-stimulating hormone index, thyrotroph thyroxine resistance index, and thyroid feedback quantile-based index (TFQI) were calculated to determine thyroid hormone sensitivity. Finally, multivariable logistic regression, generalized additive models, and subgroup analysis were performed to detect the association between sensitivity to thyroid hormone indices and the risk of OP in these patients.

Results: We did not observe a statistically significant linear relationship between sensitivity to thyroid hormones indices and OP after covariate adjustment. However, a nonlinear relationship existed between TFQI and the prevalence of OP. The inflection point of the TFQI was at -0.29. The effect sizes (odds ratio) on the left and right of the inflection point were 0.07 [95% confidence interval (CI): 0.01-0.71; p = 0.024] and 2.78 (95% CI: 1.02-7.58; p = 0.046), respectively. This trend was consistent in older female patients with higher body mass index (BMI; 25-30 kg/m²).

Conclusion: An approximate U-shaped relationship was observed between sensitivity to thyroid hormone indices and OP risk in euthyroid patients with T2DM with variations in sex, age, and BMI. These findings provide a new perspective to elucidate the role of thyroid hormones in OP, specifically in patients with T2DM.

Background: Metformin is a potent antiglycemic agent, but its importance has receded owing to the launch of novel antidiabetic medications. The benefit of metformin includes not only blood sugar control but also anti-inflammation, autophagy activation, and neuroprotection. This study investigated the risk of cardiovascular disease (CVD) in people with type II diabetes mellitus (T2DM) who adhered to metformin after adding on a second-line antiglycemic agent.

Objectives: The purpose of this study was to investigate the benefits of metformin in CVD prevention in patients with T2DM.

Design: We designed the study by comparing the incident rate of CVD events in patients with T2DM who received metformin continually and who ceased metformin during 2002-2014.

Methods: Medical information was obtained from the National Health Insurance Research Database, and patients with T2DM receiving second-line antiglycemic agents were categorized into metformin-adherent and nonadherent groups according to prescription claims. The study outcomes were the incidence of CVD hospitalization, including stroke (ischemic and hemorrhagic) and myocardial infarction (MI).

Results: A total of 31,384 patients with T2DM constituted the metformin-adherent group and were 1:1 matched to nonadherent patients. Metformin adherence was associated with a lower risk of hospitalization due to stroke [adjusted hazard ratio (aHR) = 0.51, 95% confidence interval (CI): 0.43-0.59, p < 0.001] and MI (aHR = 0.47, 95% CI: 0.43-0.53, p < 0.001). The risk reduction persisted in both ischemic and hemorrhagic strokes. Our subgroup analysis revealed that the protective effect on stroke and MI hospitalization persisted in metformin-adherent patients, both sexes, patients aged ⩽65 or >65 years, and patients with or without concurrent insulin treatment.

Conclusions: This study revealed that metformin adherence in patients with T2DM who required a first-line treatment may reduce the risk of subsequent CVD. Despite the availability of numerous novel antiglycemic agents, metformin adherence by patients who require a combination of antiglycemic agents provides an additional benefit of CVD protection.

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the digestive tract. The aetiology and pathogenesis of IBD are complex, which may lead to metabolic disorders. As a kind of metabolite, polyunsaturated fatty acid (PUFA) is closely related to IBD.

Objectives: The aim of this study was to explore the correlation between the serum PUFAs and the pathogenesis of IBD.

Design: The study is a hospital-based case-control study.

Methods: The serum free PUFAs of all participants, including 104 patients with IBD and 101 normal controls, were detected by liquid chromatography-mass spectrometry (LC-MS).

Results: Compared with the normal control, the levels of C18:2, α-C18:3 (ALA), ɤ-C18:3, C20:4 (AA), C20:5 (EPA), ω-3 C22:5, ω-6 C22:5 and C22:6 (DHA) PUFAs in patients with Crohn's disease (CD) were obviously decreased. However, in patients with ulcerative colitis (UC), the levels of AA, EPA, ω-3 C22:5, ω-6 C22:5 and DHA were downregulated. The concentrations of seven PUFAs were significantly downregulated in the active CD group. In addition, four PUFAs had comparatively higher levels in the remission UC group.

Conclusion: The present study revealed substantial differences in the levels of serum fatty acids between normal controls and patients with IBD. In detail, patients with CD were deficient in PUFAs, including the essential fatty acids. Moreover, as the disease activity aggravated, some PUFAs decreased dramatically.

Background: Apremilast, an oral phosphodiesterase 4 inhibitor, is approved in the European Union for the treatment of moderate-to-severe chronic plaque psoriasis in adult patients refractory or contraindicated to or intolerant of other systemic therapies.

Objectives: The APPRECIATE study assessed apremilast use in real-world practice and its clinical value to physicians and patients. APPRECIATE was a multinational, observational, retrospective, cross-sectional study.

Methods: Apremilast effectiveness at 6 (±1) months was assessed on the basis of psoriasis severity and health-related quality-of-life scores and treatment satisfaction using physician/patient-reported outcomes, respectively. We report the Austrian cohort of 72 patients.

Results: At 6 (±1) months, three-quarters of patients remained on apremilast, while physicians and patients reported treatment benefits across all psoriasis symptoms and manifestations. Of patients, the majority were satisfied with their treatment and achieved treatment goals considered most relevant. Patients' and physicians' perceptions of treatment effectiveness were aligned, and health-related quality-of-life scores indicated an improvement in the majority of patients. Apremilast tolerability was consistent with the known safety profile.

Conclusions: Among psoriasis patients receiving apremilast in Austria, improvement in clinical outcomes were observed and satisfaction with apremilast treatment among patients and physicians was high.

Registration: ClinicalTrials.gov NCT02740218.

Ocular imaging plays an irreplaceable role in the evaluation of eye diseases. Developing cellular-resolution ophthalmic imaging technique for more accurate and effective diagnosis and pathogenesis analysis of ocular diseases is a hot topic in the cross-cutting areas of ophthalmology and imaging. Currently, ocular imaging with traditional optical coherence tomography (OCT) is limited in lateral resolution and thus can hardly resolve cellular structures. Conventional OCT technology obtains ultra-high resolution at the expense of a certain imaging range and cannot achieve full field of view imaging. In the early years, Time-domain full-field OCT (TD-FF-OCT) has been mainly used for ex vivo ophthalmic tissue studies, limited by the low speed and low full-well capacity of existing two-dimensional (2D) cameras. The recent improvements in system design opened new imaging possibilities for in vivo applications thanks to its distinctive optical properties of TD-FF-OCT such as a spatial resolution almost insensitive to aberrations, and the possibility to control the curvature of the optical slice. This review also attempts to look at the future directions of TD-FF-OCT evolution, for example, the potential transfer of the functional-imaging dynamic TD-FF-OCT from the ex vivo into in vivo use and its expected benefit in basic and clinical ophthalmic research. Through non-invasive, wide-field, and cellular-resolution imaging, TD-FF-OCT has great potential to be the next-generation imaging modality to improve our understanding of human eye physiology and pathology.

Background: Metabolic-associated fatty liver disease (MAFLD) has become an important cause of liver cancer. The current understanding of MAFLD-related liver cancer is not sufficient, however.

Objective: The objective of this study was to investigate the clinical and metabolic characteristics of inpatients with MAFLD-related liver cancer.

Design: This is a cross-sectional investigation.

Methods: An investigation was conducted to collect the cases of hepatic malignant tumor hospitalized in Beijing Ditan Hospital, Capital Medical University from 1 January 2010 to December 31 2019. The basic information, medical history, laboratory examination results, and imaging examination results of 273 patients diagnosed with MAFLD-related liver cancer were recorded. The general information and metabolic characteristics of patients with MAFLD-related liver cancer were analyzed.

Results: In total, 5958 patients were diagnosed with hepatic malignant tumor. Among them, liver cancer due to other causes accounted for 6.19% (369/5958), MAFLD-related liver cancer was diagnosed in 273 cases of them. From 2010 to 2019, MAFLD-related liver cancer showed an increasing trend. Among 273 patients with MAFLD-related liver cancer, 60.07% were male, 66.30% were ⩾60 years old, and 43.22% had cirrhosis. The 273 patients were comprised by 38 patients with evidence of fatty liver and 235 patients without evidence of fatty liver. There was no significant difference in the proportions of sex, age, overweight/obesity, type 2 diabetes, and the presence of ⩾2 metabolic-related factors between the two groups. In the group without evidence of fatty liver, 47.23% patients had cirrhosis, which was significantly higher than 18.42% in the group with evidence of fatty liver (p < 0.001).

Conclusion: MAFLD-related liver cancer should be considered in liver cancer patients with metabolic risk factors. Half of MAFLD-related liver cancer occurred in the absence of cirrhosis.

Background: Corneal fluorescein sodium staining is a valuable diagnostic method for various ocular surface diseases. However, the examination results are highly dependent on the subjective experience of ophthalmologists.

Objectives: To develop an artificial intelligence system based on deep learning to provide an accurate quantitative assessment of sodium fluorescein staining score and the size of cornea epithelial patchy defect.

Design: A prospective study.

Methods: We proposed an artificial intelligence system for automatically evaluating corneal staining scores and accurately measuring patchy corneal epithelial defects based on corneal fluorescein sodium staining images. The design incorporates two segmentation models and a classification model to forecast and assess the stained images. Meanwhile, we compare the evaluation findings from the system with ophthalmologists with varying expertise.

Results: For the segmentation task of cornea boundary and cornea epithelial patchy defect area, our proposed method can achieve the performance of dice similarity coefficient (DSC) is 0.98/0.97 and Hausdorff distance (HD) is 3.60/8.39, respectively, when compared with the manually labeled gold standard. This method significantly outperforms the four leading algorithms (Unet, Unet++, Swin-Unet, and TransUnet). For the classification task, our algorithm achieves the best performance in accuracy, recall, and F1-score, which are 91.2%, 78.6%, and 79.2%, respectively. The performance of our developed system exceeds seven different approaches (Inception, ShuffleNet, Xception, EfficientNet_B7, DenseNet, ResNet, and VIT) in classification tasks. In addition, three ophthalmologists were selected to rate corneal staining images. The results showed that the performance of our artificial intelligence system significantly outperformed the junior doctors.

Conclusion: The system offers a promising automated assessment method for corneal fluorescein staining, decreasing incorrect evaluations caused by ophthalmologists' subjective variance and limited knowledge.

Background: Which noninvasive brain stimulation (NIBS) treatment - transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS) - is more beneficial for stroke patients' cognitive rehabilitation is still up for debate.

Objectives: Our goal is to provide an overview of the research on the effectiveness and safety of various NIBS protocols.

Design: Systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs).

Methods: This NMA compared any active NIBS versus sham stimulation in adult stroke survivors to enhance cognitive function, with a focus on global cognitive function (GCF), attention, memory, and executive function (EF) using the databases MEDLINE, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. The NMA statistical approach was built on a frequency framework. The effect size was estimated by the standardized mean difference (SMD) and a 95% confidence interval (CI). We compiled a relative ranking of the competing interventions based on their surface under the cumulative ranking curve (SUCRA).

Results: NMA showed that high-frequency repeated TMS (HF-rTMS) improved GCF compared with sham stimulation (SMD = 1.95; 95% CI: 0.47-3.43), while dual-tDCS improved memory performance versus sham stimulation significantly (SMD = 6.38; 95% CI: 3.51-9.25). However, various NIBS stimulation protocols revealed no significant impact on enhancing attention, executive function, or activities of daily living. There was no significant difference between the active stimulation protocols for TMS and tDCS and sham stimulation in terms of safety. Subgroup analysis demonstrated an effect favoring activation site of the left dorsolateral prefrontal cortex (DLPFC) (SUCRA = 89.1) for enhancing GCF and bilateral DLPFC (SUCRA = 99.9) stimulation for enhancing memory performance.

Conclusion: The HF-rTMS over the left DLPFC appears to be the most promising NIBS therapeutic option for improving global cognitive performance after stroke, according to a comparison of numerous NIBS protocols. Furthermore, for patients with post-stroke memory impairment, dual-tDCS over bilateral DLPFC may be more advantageous than other NIBS protocols. Both tDCS and TMS are reasonably safe.

Registration: PROSPERO ID: CRD42022304865.